Download Leukaemia Section t(7;9)(q34;q32) Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Leukaemia Section
Mini Review
t(7;9)(q34;q32)
Jacques Boyer
Laboratoire d'Hématologie, CH du MANS, France (JB)
Published in Atlas Database: November 2002
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0709q34q32ID1056.html
DOI: 10.4267/2042/37935
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2003 Atlas of Genetics and Cytogenetics in Oncology and Haematology
duplicated and translocated to the chromosome 9 at
9p21.
Protein
T cell receptor beta chains.
Clinics and pathology
Disease
Specifically associated with T-cell acute lymphoblastic
leukemia (T-ALL).
TAL2
Epidemiology
Location
9q32
DNA/RNA
The TAL2 gene is located at q32.
Protein
TAL2 potentially encodes a basic helix-loop-helix
(bHLH) phosphoprotein (size 108 amino acids) that is
highly related to those specified by TAL1 and LYL1
also implicated in T-ALL. The bHLH protein interacts
with the product of RBTN1 and RBTN2 (cysteine-rich
LIM motifs).
The t(7;9)(q34;q32) is present in two cases of a serie of
5 patients with 7q34 involvment.
Clinics
Children with large mediastinal mass.
Cytology
The hematological feature of the T-ALL with
rearrangement of 7q34 shows high WBC (range 95 to
400 x 109/L).
Cytogenetics
Result of the chromosomal
anomaly
Cytogenetics morphological
9q32 is a partner of 7q34. The other partners are 1p34,
1p32, 9q34, 10q24, 11p13, 15q22 and 19p13.
Hybrid gene
Additional anomalies
Description
TAL2 is transcriptionaly activated by t(7;9)(q34;q32)
in T-ALL. The chromosome 9 breakpoints of the
t(7;9)(q34;q32) occur 33 kbp downstream of sequences
that encode the TAL2 HLH domain. Translocated
TAL2 are juxtaposed with transcriptional regulatory
elements within the T-cell receptor beta-chain locus.
del(6)(q21), del(4)(q31q35).
Genes involved and proteins
TCRB (T-cell receptor beta-chain)
Location
7q35
DNA/RNA
The TRB locus at 7q35 spans 685 kb. The locus
contains 2 types of coding elements: TCR elements
(64-67 variable genes TRBV, 2 clusters of diversity,
joining and constant segments) and 8 trypsinogen
genes. A portion of the TCRB locus has been
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(1)
Fusion protein
Note
No fusion protein.
Oncogenesis
The TAL2 transcription is activated ectopically in
lymphoid cells and the inappropriate expression of
39
t(7;9)(q34;q32)
Boyer J
rearrangements of chromosome 7 band q34. Blood. 1988
Feb;71(2):395-402
TAL2 in these cells promotes development of T-ALL.
Normaly, the TAL genes are not expressed in the
thymus. The TAL genes become activated and
expressed in the thymus upon chromosomal
translocation which ultimately leads to the development
of T-ALL.
The (7;9) translocation express a TAL2 gene product of
108 amino acids. In leukemic cells this product exists
in both a phosphorylated and an unphosphorylated
form. Serine residue 100 is the major site of TAL2
phosphorylation in vivo. And it serves as an effective in
vitro substrate for MAP kinases such as ERK1.
TAL2 polypeptides interact in vivo with the E2A gene
products to form HLH heterodimers that bind DNA, the
result is the E2A inactivation. The E2A products are
transcriptional factors implicated in the B and T cell
development.
TAL2 product was also shown to bind with a GTP
binding protein (DRG). The properties of TAL2
broadly resemble those described previously for TAL1
and therefore support the idea that both encoded
proteins promote T-ALL by a common mechanism and
the malignant potential of these proteins is likely to
reside within their HLH domains though the
inactivation of E2A.
Xia Y, Brown L, Yang CY, Tsan JT, Siciliano MJ, Espinosa R
3rd, Le Beau MM, Baer RJ. TAL2, a helix-loop-helix gene
activated by the (7;9)(q34;q32) translocation in human T-cell
leukemia. Proc Natl Acad Sci U S A. 1991 Dec
15;88(24):11416-20
Secker-Walker LM, Campana D, Hawkins JM, Sampson RE,
Coustan-Smith E. Karyotype and T-cell receptor expression in
T-lineage acute lymphoblastic leukemia. Genes Chromosomes
Cancer. 1992 Jan;4(1):41-5
Baer R. TAL1, TAL2 and LYL1: a family of basic helix-loophelix proteins implicated in T cell acute leukaemia. Semin
Cancer Biol. 1993 Dec;4(6):341-7
Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH,
Baer R. Specific in vivo association between the bHLH and
LIM proteins implicated in human T cell leukemia. EMBO J.
1994 Oct 17;13(20):4831-9
Xia Y, Hwang LY, Cobb MH, Baer R. Products of the TAL2
oncogene in leukemic T cells: bHLH phosphoproteins with
DNA-binding activity. Oncogene. 1994 May;9(5):1437-46
Cytogenetic abnormalities in adult acute lymphoblastic
leukemia: correlations with hematologic findings outcome. A
Collaborative Study of the Group Français de Cytogénétique
Hématologique. Blood. 1996 Apr 15;87(8):3135-42
Mahajan MA, Park ST, Sun XH. Association of a novel GTP
binding protein, DRG, with TAL oncogenic proteins. Oncogene.
1996 Jun 6;12(11):2343-50
To be noted
Bain G, Engel I, Robanus Maandag EC, te Riele HP, Voland
JR, Sharp LL, Chun J, Huey B, Pinkel D, Murre C. E2A
deficiency leads to abnormalities in alphabeta T-cell
development and to rapid development of T-cell lymphomas.
Mol Cell Biol. 1997 Aug;17(8):4782-91
Case Report
Translocation t(7;9)(q34;q32) found in pediatric T-cell
acute lymphoblastic leukemia.
This article should be referenced as such:
References
Boyer J. t(7;9)(q34;q32). Atlas Genet Cytogenet Oncol
Haematol. 2003; 7(1):39-40.
Smith SD, Morgan R, Gemmell R, Amylon MD, Link MP, Linker
C, Hecht BK, Warnke R, Glader BE, Hecht F. Clinical and
biologic
characterization
of
T-cell
neoplasias
with
Atlas Genet Cytogenet Oncol Haematol. 2003; 7(1)
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